Toxicology Research最新文献

Iodide organic compounds, the conversion reaction by-products in shale gas wastewater, have potential risks to ecological environment and human health. However, information about their negative effects and molecular mechanism remains limited. In this study, three typical iodoalkanes (C₂H₅I, C₂H₄I₂, and C₃H₆I₂) identified in shale gas wastewater from Chongqing of China were utilized to investigate their cytotoxicity and potential mechanisms in Hela cells. Results showed that three iodoalkanes reduced cell proliferation in a dose-dependent manner, and cytotoxicity of di-iodoalkanes (C₂H₄I₂ and C₃H₆I₂) was stronger than that of mono-iodoalkanes (C₂H₅I). Furthermore, C₂H₄I₂ and C₃H₆I₂ significantly decreased colony formation of HeLa cells, accompanying by disorder of cell cycle checkpoint genes (CyclinA2, CyclinD1, CyclinE1, CDK2 and p21). Three iodoalkanes stimulated production of intracellular ROS, caused GSH/GSSG ratio decrease, MMP loss, and promoted expression of NRF2, HO-1 and NQO-1. Additionally, C₂H₄I₂ and C₃H₆I₂ induced cell membrane damage, cell apoptosis and enhanced expression of apoptosis markers (Caspase-3, Caspase-8, Cyt-c, and p53). Combined use of antioxidant NAC obviously alleviated the toxic effects of iodoalkanes, including cell proliferation inhibition, oxidative stress and apoptosis induction. Generally, iodoalkanes might suppress cell proliferation via inhibiting cycle progression from G₁ to S phase, inducing mitochondrial apoptosis, which was closely related to oxidative stress-mediated mitochondrial damage.

In the agriculture sector, insects and pests are major constraints to increased global food production. With the advancement in genetic engineering, transgenic crops expressing insecticidal proteins are increasingly prevalent in agriculture having the advantages of being eco-friendly over the non-conventional, synthetic insecticides and pesticides, yet concerns persist regarding their safety, particularly on non-target organisms which necessitate to address thorough investigation before widespread commercialization. The current study was aimed to evaluate the toxicity of Vip3Aa86-expressing transgenic maize in Wistar rats. The presence of Vip3Aa86 gene in maize plants was confirmed through PCR and protein quantification was done through ELISA. Comprehensive histopathological examination, blood chemistry, serum chemistry, urine chemistry and molecular analysis of apoptosis and immunity-related genes were done to evaluate any adverse effects on rats. Results indicated no significant differences in growth, organ weights, hematology, serum, urine chemistry, and gene expression analysis between rats fed with transgenic maize diets and control except for a few variations. PCR amplification of DNA isolated from rats' blood and vital organs did not show transgene amplification in any group. These findings conclude that the consumption of transgenic maize expressing the Vip3Aa86 gene does not pose immediate hazards to rat health under the conditions tested, supporting its regularity approval for commercial use.

Bis-(2-ethylhexyl) phthalate commonly called (DEHP) is a major environmental contaminant known to interfere with various biological pathways following human exposure. Our previous research demonstrated that Bis(2-ethylhexyl) phthalates increased the oxidative stress, increased level of acetylcholinesterase in third instar larvae of Drosophila melanogaster (hsp70-lacZ) Bg. ⁹ This study demonstrated that apigenin, a naturally occurring flavonoid, effectively mitigates the toxic effects of DEHP in third instar larvae. In this study, apigenin was incorporated into the diet at final concentrations of 20, 40, 60, and 80 μM, along with 0.02 M Bis-(2-ethylhexyl) phthalate. The larvae were exposed to this diet for a period of 24 h. Through metabolites study and biochemical evaluations, we assessed the impact of apigenin on oxidative stress markers, enzymatic activity, and metabolic pathway alterations in the larvae exposed to Bis-(2-ethylhexyl) phthalate. Our results indicated that Bis-(2-ethylhexyl) phthalate exposure along with apigenin significantly affected oxidative stress markers, leading to increased levels of glutathione (GSH) and decreased activities of superoxide dismutase (SOD), and catalase (CAT). Furthermore, Bis-(2-ethylhexyl) phthalate along with apigenin exposure was associated with decreased in lipid peroxidation (as indicated by TBARS), protein carbonylation (PC) highlighting extensive oxidative damage. Metabolomic analysis revealed notable changes in critical metabolites, and apigenin was found to mitigate oxidative stress and also changes in the concentration of certain metabolities. This study highlights the potential of apigenin a protective compound against Bis-(2-ethylhexyl) phthalate-induced toxicity by alleviating oxidative stress and helping to restore metabolic balance.

The widespread use of pyrethroid insecticides poses a public health hazard, and previous studies have shown that these insecticides may contribute to liver injury, but the mechanism of action has not been comprehensively investigated. The differentially expressed genes in the GSE102006 dataset and the targets from the GeneCards and OMIM databases were used as relevant targets for drug-induced liver injury (DILI). These targets were intersected with the predicted targets of pyrethroids, and 167 intersecting targets were obtained for protein-protein interaction (PPI) analysis and enrichment analysis. The PPI network consists of 1,378 edges. SRC, NFKB1, MAPK3, RELA are key targets in the network. Pathway enrichment showed that the intersection targets were significantly enriched in cAMP, calcium, PI3K-Akt, and VEGF signaling pathways. These signaling pathways extensively regulate cell growth, reproduction, apoptosis, and mediate inflammatory responses. In addition, this study identified a causal relationship between gene variants in PIM1 and FDFT1 and disease progression by mendelian randomization analysis. The results of molecular docking and molecular dynamics simulation further verify the strong and stable interaction between pyrethroids and these potential targets, suggesting their possible role in the mechanism of pyrethroid-related liver injury. These findings provide a theoretical foundation for future research into biomarkers of pyrethroid-induced DILI.

Inflammation is the primary response to any sort of injury that provokes an immune system and release of inflammatory mediators. The aim of current study is to explore the anti-inflammatory and therapeutic potential of Carica papaya against inflammation caused by environmental particles i.e. silica, dust, and asbestos in rats. The study included four groups (G1 NC, G2 PC, G3 M.T and G4 H.T) with each having eight male albino rats raised for the period of 14 days. Rats were decapitated on day 14^th and sampling was done for CBC, serum analysis, qTR PCR, and histopathology. Data analysis was done through ANOVA and Tukey's Test. There was significant (P ≤ 0.05) decrease of diffrential leucoctyic cells count in H.T group as compared to PC group. Serum lipid profile showed siginificant (P ≤ 0.05) reduction of choltesrol, triglyceride, and LDL, while enhanced HDL concentration in H.T and M.T groups as comparision to PC group. Heat map was generated for gene expression through qRT PCR which revealed the significant (P ≤ 0.05) up-regulation of IL-1 beta, IL-6, IL-33, IL-17, INF-gamma, TNF alpha, TLR-4, Traf-4 and Traf-6. Whereas IL-4, IL-10, and IGF-1 were being significantly (P ≤ 0.05) down- regulated in PC and increased in M.T and H.T groups. Microscopic examination exhibits distorted parenchyma and destructed walls of alveoli in PC while restoration of parenchyma and alveolar structure was seen in treatment groups. It was concluded that C. papaya has potent anti-inflammatory and mitigate the oxidative stress due to inflammation.

Quorum-sensing (QS), a bacterial communication mechanism regulating virulence, biofilm formation, and environmental adaptation, represents a promising target for antivirulence therapies. Unlike conventional antibiotics, QS inhibition disrupts bacterial coordination without promoting antimicrobial resistance. Marine actinobacteria, well adapted to extreme habitats, are a rich source of bioactive quorum-sensing inhibitors (QSI). This study evaluates the QSI activity of ethyl acetate (EA) extract from a marine actinobacterium, Streptomyces rubrogriseus, against Chromobacterium violaceum 12472, a QS model organism. Marine actinobacteria were isolated from Kochi coastal sediments, and the most potent strain was identified via 16S rDNA sequencing. Crude extract was prepared through solid-state fermentation and solvent extraction. Antivirulence assays included MIC determination, violacein inhibition, biofilm suppression, AHL quantification, and swarming motility tests. Gene expression changes were analyzed by RT-qPCR, while bioactive metabolites were fractionated using silica gel chromatography and characterized by HR-LC-MS. In silico approaches, including molecular docking and molecular dynamics (MD) simulations, were applied to predict compound-receptor interactions. The extract showed a MIC of 128 μg/mL. At 64 μg/mL (sub-MIC), it inhibited biofilm formation (92%), violacein production (78%), and AHL levels (74%), while impairing motility. RT-qPCR confirmed downregulation of the QS-regulated cviR gene. HR-LC-MS profiling identified several metabolites, among which 3-dehydrosphinganine exhibited the highest docking affinity for the CviR receptor (Glide score - 9.688 kcal/mol). MD simulations further validated binding stability of 3-dehydrosphinganine and hexadecasphinganine. These findings highlight marine actinobacteria-derived metabolites as potent QS inhibitors with significant antivirulence potential.

This study investigated heavy metal contamination in Clarias gariepinus, Oreochromis niloticus, and water from the polluted Ala River using atomic absorption spectroscopy. Carcinogenic and non-carcinogenic risks were assessed per USEPA guidelines. DNA damage in fish was evaluated via micronucleus assay and nuclear aberration analysis, with Alanine aminotransferase (ALT), Aspartate Aminotransferase (AST), and Alkaline Phosphatase (ALP) activities examined for potential mechanisms. Cadmium (Cd), Chromium (Cr), Nickel (Ni), and Lead (Pb) levels in fish and water exceeded WHO/FAO limits, with higher concentrations in C. gariepinus. Health risk assessments showed that estimated daily intake (EDI) of these metals in children and adults exceeded safe limits, particularly from C. gariepinus consumption. Consumption of Ala river water posed health risks, as Cd and Pb EDI values exceeded safe limits for adults and children. High hazard index levels in C. gariepinus, O. niloticus, and water indicated non-carcinogenic risks, while total cancer risk values surpassed the threshold (>10^-4), signifying significant cancer risks. DNA damage analysis showed a statistically significant (p ≤ 0.05) increase in micronuclei (MN) and other nuclear aberrations, with higher MN frequency in C. gariepinus. ALT, AST, and ALP levels were elevated, indicating physiological stress. The study underscores severe metal contamination in Ala River, urging stricter pollution control measures.

The investigation delves into biological interactions of CuO-NPs throughout study focusing on their synthetic structure together with their functional characteristics and their dangerous nature. The production of CuO-NPs happened when copper (II) sulfate pentahydrate underwent a chemical reduction process with D-glucose under NaOH conditions to stabilize pH levels. Structural and chemical evaluations used SEM, XRD and FTIR as their analytical techniques. Male albino mice received 15 mg/kg (low dose, NPS-L) and 30 mg/kg (high dose, NPS-H) for 28 days, through which researchers evaluated toxicological effects. The investigators measured blood cell counts together with serum lipids, liver and kidney enzyme assays. Significant dose-oriented toxic behavior of CuO-NPs led to substantial variations in WBCs, RBCs, and hemoglobin, along with organ function test results. The microscopic evaluation of high-dose groups showed necrosis together with glomerular destruction and inflammatory findings. Male albino mouse exposure to low and high doses for 28 days decreased both catalase and superoxide dismutase activity levels. Pharmacokinetic studies demonstrated that CuO-NPs exhibited moderate solubility together with small blood-brain barrier permeability and minimal metabolic enzyme disruption, thus indicating limited circulation and avoidance of neurotoxicity. Toxicity screenings demonstrated that substance produced negligible harm to liver tissues and hearts and had low toxicity for aquatic life while showing minimal impact on endocrine system. While CuO-NPs present opportunities in biomedical sector research, they prove toxic at different dosage levels and require additional research for safe medical deployment. Research shows that CuO-NPs require thorough preclinical evaluation regarding their biological accessibility and safety standards before biomedical and environmental applications can be employed.

Alzheimer's disease (AD) is a progressive, chronic disease characterized by impaired cognitive function. Currently, there is no complete cure for ad; current treatments are aimed at reducing symptoms and slowing the progression of the disease. It is thought that the amount of fatty acid consumption and the balance between them may be protective against neurological diseases. In this study, it was aimed to determine the protective effects of Ω3/Ω6 polyunsaturated fatty acids ratios in Aβ_1-42-induced ad model in human neuroblastoma (SH-SY5Y) cells. The viability of cells was determined by MTT assay. The percentage of apoptotic cells was determined by FITC-conjugated Annexin-V/PI. ROS, MMP and cell cycle analysis were performed by flow cytometry. The amount of acetylcholinesterase enzyme was measured with a commercial kit. 48 h after the application, a statistically significant decrease was observed in the MTT test in the 1/1, 1/2 and 1/8 groups and in the amount of AChE in the 1/4, 1/8 and 1/16 groups. According to apoptosis findings, all ratios were observed to reduce cell viability compared to the control group. ROS and MMP levels were detected to decrease in all groups compared to the control group. The highest neuroprotective effect against oxidative stress was observed at 1/1 dose. Aβ_1-42 induced blockade of the cell cycle was observed to be partially corrected by 1/8 dose. As a result, it can be said that Ω6 and Ω3 fatty acids, when used in 1/4 and 1/8 doses can provide a protective effect against Alzheimer's disease.

The protective effects of sevoflurane (Sev) in cardiovascular disease have been well documented in studies. The investigation aimed to clarify the contribution of miR-1291 to the pathophysiological process of hypoxia-reoxygenation (H/R)-induced cardiomyocyte injury in the setting of Sev preconditioning. H/R cell models were constructed with AC16 cells and the cell models were pretreated with 1%, 1.5% and 2% concentrations of Sev. Quantitative reverse transcription polymerase chain reaction was performed to detect miR-1291 and NF2 expression in cells. Cell viability was assessed using the cell counting kit-8 assay. Apoptosis was evaluated via flow cytometry. Cellular cardiac troponin I (cTnI), lactate dehydrogenase (LDH), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels were detected by enzyme-linked immunosorbent assay. Dual luciferase reporter gene assay and RIP analysis were applied to validate the binding of miR-1291 to NF2. In the H/R cell model, miR-1291 was downregulated, and this was accompanied by reduced cell viability, increased apoptosis, and elevated levels of cTnI, LDH, IL-6 and TNF-α. In contrast, inhibition of miR-1291 expression impaired the protective effect of Sev on cardiomyocytes. NF2 was a downstream target gene of miR-1291, and miR-1291 negatively regulated the expression of NF2. Knockdown of NF2 expression alleviated the effects of miR-1291 inhibition on Sev-treated cells. Sev attenuates H/R-induced cardiomyocyte injury by regulating miR-1291/NF2 expression and inhibiting apoptosis and inflammatory responses. This study unveils a novel mechanism of Sev-mediated myocardial protection, offering theoretical support and potential therapeutic targets for myocardial injury prevention and treatment.